The purpose of this study is to develop techniques for studying central nervous system monoamine metabolism in man, and to carry out pharmacokinetic studies of psychoactive drugs. Studies of the kinetics and clearance of deuterated homovanillic acid (HVA) from the circulation continue in rhesus monkeys and patients. Problems with the application of this technique to study CNS dopamine turnover in man were resolved by further study of the kinetics and volume distribution of the metabolite, HVA, before and after probenecid administration. A GC-MS assay for dopamine sulfate (DASO4) was utilized to study DASO4 as a metabolite of dopamine in the circulation and in CSF. The concentration of conjugated DA in serum is 20 - 30 picomoles/ml. Levels of free dopamine in lateral ventricle CSF are approximately 0.75 picomole/ml, while conjugated DA is 2 - 3 picomoles/ml. DASO4 does not appear to cross the blood-brain barrier. A pharmacokinetic study of phencyclidine (PCP) was carried out in the monkey. The plasma concentration - time curve for PCP is described by a two compartment model with a terminal half-life of 200 minutes. Assay for the 4-OH-piperidine and 4-OH-cyclohexanol metabolite were developed.